Featured Research

from universities, journals, and other organizations

Holding back immunity: 'Gatekeeper' protein key to helping immune cells to sound warning

Date:
February 3, 2012
Source:
RIKEN
Summary:
A 'gatekeeper' protein plays a critical role in helping immune cells to sound a warning after encountering signs of tumor growth or infection, researchers report.

A 'gatekeeper' protein plays a critical role in helping immune cells to sound a warning after encountering signs of tumor growth or infection.

Related Articles


When the body's own cells turn into ticking time bombs, as in cases of viral infection or cancerous transformation, a mechanism known as 'cross-presentation' enables the immune system's dendritic cells (DCs) to sound the alarm.

"Dendritic cells first internalize cancerous or virus-infected cells through a mechanism called phagocytosis, and then process cellular antigens into short peptides," explains Heiichiro Udono of the RIKEN Center for Allergy and Immunology in Yokohama. DCs subsequently present these fragments to killer T cells, which seek out and destroy other affected cells. Phagocytosed molecules travel within sealed membrane bubbles called endosomes, and new work from Udono and his colleagues has revealed insights into how these antigens are released into the cytosol prior to cross-presentation.

Udono's team focused on heat-shock protein 90 (HSP90), a molecule that previous studies have linked to cross-presentation. HSP90 comes in two forms, α and β, which perform overlapping roles. Mice need at least one of these proteins to live. Udono and colleagues succeeded in generating healthy mice that exclusively lack HSP90α. They found that, although HSP90β appears to make some contribution, the loss of HSP90α had a striking effect on antigen processing. DCs isolated from these mice showed defects in their capacity for cross-presentation, and failed to activate killer T cells efficiently following exposure to ovalbumin, a model antigen.

HSP90α-deficient DCs proved perfectly capable of internalizing ovalbumin within endosomes; however, they generally failed to release this antigen into the cytosol. The researchers noted a similar effect after treating genetically normal DCs with a chemical that inhibits HSP90α, confirming the central role of this protein in endosomal release.

Udono and colleagues further demonstrated the extent of these defects by injecting HSP90α-deficient mice with cytochrome c, a protein that selectively eliminates a subpopulation of DCs after being taken up and released into the cytosol. Strikingly, cytochrome c treatment had a dramatically reduced effect on DCs from mutant mice relative to their wild-type counterparts. "This is the most sensitive in vivo assay to show antigen translocation to the cytosol," says Udono. "This phenomenon was absent in HSP90α knockout mice, which makes me confident that our finding is important and has physiological relevance."

Accordingly, Udono believes that molecules that modulate HSP90 activity might help clinicians to boost a patient's immune counterattack against infection or cancer. "If we can control the expression levels of HSP90 and other heat shock proteins," he says, "it could be of great benefit to human health."

The corresponding author for this highlight is based at the Laboratory for Immunochaperones, RIKEN Research Center for Allergy and Immunology.


Story Source:

The above story is based on materials provided by RIKEN. Note: Materials may be edited for content and length.


Journal Reference:

  1. T. Imai, Y. Kato, C. Kajiwara, S. Mizukami, I. Ishige, T. Ichiyanagi, M. Hikida, J.-Y. Wang, H. Udono. Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells. Proceedings of the National Academy of Sciences, 2011; 108 (39): 16363 DOI: 10.1073/pnas.1108372108

Cite This Page:

RIKEN. "Holding back immunity: 'Gatekeeper' protein key to helping immune cells to sound warning." ScienceDaily. ScienceDaily, 3 February 2012. <www.sciencedaily.com/releases/2012/02/120203090813.htm>.
RIKEN. (2012, February 3). Holding back immunity: 'Gatekeeper' protein key to helping immune cells to sound warning. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2012/02/120203090813.htm
RIKEN. "Holding back immunity: 'Gatekeeper' protein key to helping immune cells to sound warning." ScienceDaily. www.sciencedaily.com/releases/2012/02/120203090813.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Reuters - Light News Video Online (Dec. 19, 2014) Millions of monarch butterflies begin to descend onto Mexico as part of their annual migration south. Rough Cut (no reporter narration) Video provided by Reuters
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com
Birds Might Be Better Meteorologists Than Us

Birds Might Be Better Meteorologists Than Us

Newsy (Dec. 19, 2014) A new study suggests a certain type of bird was able to sense a tornado outbreak that moved through the U.S. a day before it hit. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins